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Wednesday, August 12, 2015

Autism Mutation Isolated

Autism Mutation Isolated - Could Be Treated with Specific Enzyme

Seth Augenstein | August 7, 2015

Autism is a large, sprawling genetic puzzle. Researchers found as many as 1,000 genetic mutations could make up the baffling variety along the spectrum.
The mechanism at play in one of those many mutations is now on its way, according to new research published in the journal Cell.

<more at; related link: (Autism Mutation Isolated – Could Be Treated with Specific Enzyme. Auguts 10, 2015) and (UNC scientists pinpoint how a single genetic mutation increases autism risk; The research shows the precise cellular mechanisms that could increase risk for the disorder and how an existing drug might help thousands of people with autism. August 6, 2015); further: (An Autism-Linked Mutation Disables Phosphorylation Control of UBE3A. Jason J. Yi, Janet Berrios, Jason M. Newbern. William D. Snider, Benjamin D. Philpot, Klaus M. Hahn, Mark J. Zylka. showArticle Info [Summary: Deletion of UBE3A causes the neurodevelopmental disorder Angelman syndrome (AS), while duplication or triplication of UBE3A is linked to autism. These genetic findings suggest that the ubiquitin ligase activity of UBE3A must be tightly maintained to promote normal brain development. Here, we found that protein kinase A (PKA) phosphorylates UBE3A in a region outside of the catalytic domain at residue T485 and inhibits UBE3A activity toward itself and other substrates. A de novo autism-linked missense mutation disrupts this phosphorylation site, causing enhanced UBE3A activity in vitro, enhanced substrate turnover in patient-derived cells, and excessive dendritic spine development in the brain. Our study identifies PKA as an upstream regulator of UBE3A activity and shows that an autism-linked mutation disrupts this phosphorylation control. Moreover, our findings implicate excessive UBE3A activity and the resulting synaptic dysfunction to autism pathogenesis.]>

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